{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:21Z","timestamp":1787013981898,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["P\u2010CREATE \/ 21cm0106403h0006"],"award-info":[{"award-number":["P\u2010CREATE \/ 21cm0106403h0006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["P\u2010PROMOTE \/ 22ama221401h0001"],"award-info":[{"award-number":["P\u2010PROMOTE \/ 22ama221401h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,11]]},"abstract":"Abstract<\/jats:title>\n \n Mutations of\n KRAS<\/jats:italic>\n ,\n CDKN2A<\/jats:italic>\n ,\n TP53<\/jats:italic>\n , and\n SMAD4<\/jats:italic>\n are the four major driver genes for pancreatic ductal adenocarcinoma (PDAC), of which mutations of\n KRAS<\/jats:italic>\n and\n TP53<\/jats:italic>\n are the most frequently recognized. However, molecular\u2010targeted therapies for mutations of\n KRAS<\/jats:italic>\n and\n TP53<\/jats:italic>\n have not yet been developed. To identify novel molecular targets, we newly established organoids with the\n Kras<\/jats:italic>\n mutation (\n Kras<\/jats:italic>\n mu<\/jats:sup>\n OR) and\n Trp53<\/jats:italic>\n loss of function using Cre transduction and CRISPR\/Cas9 (\n Kras<\/jats:italic>\n mu<\/jats:sup>\n \/\n p53<\/jats:italic>\n mu<\/jats:sup>\n OR) from murine epithelia of the pancreatic duct in\n Kras<\/jats:italic>\n \n LSL\u2010G12D<\/jats:italic>\n <\/jats:sup>\n mice, and then analyzed the proteomic and metabolomic profiles in both organoids by mass spectrometry. Hyperfunction of the glycolysis pathway was recognized in\n Kras<\/jats:italic>\n mu<\/jats:sup>\n \/\n p53<\/jats:italic>\n mu<\/jats:sup>\n OR compared with\n Kras<\/jats:italic>\n mu<\/jats:sup>\n OR. Loss of function of triosephosphate isomerase (TPI1), which is involved in glycolysis, induced a reduction of cell proliferation in human PDAC cell lines with the\n TP53<\/jats:italic>\n mutation, but not in PDAC or in human fibroblasts without\n TP53<\/jats:italic>\n mutation. The\n TP53<\/jats:italic>\n mutation is clinically recognized in 70% of patients with PDAC. In the present study, protein expression of TPI1 and nuclear accumulation of p53 were recognized in the same patients with PDAC. TPI1 is a potential candidate therapeutic target for PDAC with the\n TP53<\/jats:italic>\n mutation.\n <\/jats:p>","DOI":"10.1111\/cas.16302","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T12:39:27Z","timestamp":1726058367000},"page":"3622-3635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Identification of\n TPI1<\/scp>\n As a potential therapeutic target in pancreatic cancer with dependency of\n \n TP53<\/i>\n <\/scp>\n mutation using multi\u2010omics analysis"],"prefix":"10.1111","volume":"115","author":[{"given":"Tomoaki","family":"Toyoda","sequence":"first","affiliation":[{"name":"Department of Bioregulation, Graduate School of Medicine Nippon Medical School Bunkyo\u2010ku Tokyo Japan"},{"name":"Department of Oral Pathobiological Science and Surgery Tokyo Dental College Tokyo 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